Istituto Oncologico Veneto-IRCCS, Medical Oncology 1 - Via Gattamelata, 64, 35128 Padova, Italy.
Anticancer Res. 2013 Aug;33(8):3487-94.
Bevacizumab has provided encouraging results in relapsed glioblastoma multiforme (GBM). Pre-clinical and clinical investigations also showed that continuous low-dose temozolomide has some antiangiogenic activity. Based on this evidence, a phase II trial was designed to investigate an oral regimen of sorafenib, an oral multikinase inhibitor, and metronomic temozolomide for relapsed GBM.
Forty-three patients (median age=60.0 years) naive for antiangiogenic agents received 400 mg sorafenib twice daily plus TMZ 40 mg/m(2)/day until disease progression.
Toxicity, mostly grade 1-2, was manageable. Grade 3-4 toxicities were hand-foot syndrome (n=4), hypertension (n=2), and fatigue (n=3). Five patients (12%) achieved partial response, 18 (43%) stable disease, 20 (48%) showed progression. The median time-to-progression was 3.2 months, 6-month progression-free survival was 26%, and median overall survival was 7.4 months.
This combination of sorafenib and temozolomide was feasible and safe, showing some activity in patients with relapsed GBM.
贝伐单抗在复发性多形性胶质母细胞瘤（GBM）中提供了令人鼓舞的结果。临床前和临床研究还表明，持续低剂量替莫唑胺具有一定的抗血管生成活性。基于这一证据，设计了一项 II 期试验，以研究复发性 GBM 的索拉非尼（一种口服多激酶抑制剂）和替莫唑胺节拍治疗方案。
43 名（中位年龄=60.0 岁）对血管生成抑制剂呈初始状态的患者接受 400 mg 索拉非尼每日两次联合 TMZ 40 mg/m2/天，直至疾病进展。
毒性可管理，主要为 1-2 级。3-4 级毒性为手足综合征（n=4）、高血压（n=2）和疲劳（n=3）。5 名患者（12%）达到部分缓解，18 名（43%）病情稳定，20 名（48%）病情进展。中位无进展生存期为 3.2 个月，6 个月无进展生存率为 26%，中位总生存期为 7.4 个月。
索拉非尼联合替莫唑胺是可行且安全的，在复发性 GBM 患者中显示出一定的活性。
